Pharmacokinetics and metabolism of the flavonoid scutellarin in humans after a single oral administration

doi:10.1124/dmd.106.009779

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	Pharmacokinetics and metabolism of the flavonoid scutellarin in humans after a single oral administration
	Chen, Xiaoyan; Cui, Liang ; Duan, Xiaotao ; Ma, Bin ; Zhong, Dafang
刊名	DRUG METABOLISM AND DISPOSITION
	2006-08
卷号	34 期号:8 页码:1345-1352
ISSN号	0090-9556
DOI	10.1124/dmd.106.009779
文献子类	Article
英文摘要	Scutellarin is widely used in treating various cardiovascular diseases. Few data are available regarding its metabolism and pharmacokinetics in humans. The objectives of this study were to develop methods to identify major metabolites of scutellarin in human urine and plasma and to determine simultaneously the parent drug and its major metabolites in human plasma for pharmacokinetic studies. Four metabolites were detected in urine samples by liquid chromatography coupled with electrospray multistage mass spectrometry (MS), but only one of them was found in plasma. Its structure was confirmed as scutellarein 6-O-beta-D-glucuronide by MS, NMR, and UV absorbance spectra. The plasma concentrations of scutellarin and the major metabolite were simultaneously determined using liquid chromatography- tandem MS. After a single p.o. administration of 60 mg of scutellarin to 20 healthy subjects, the plasma concentrations of scutellarin were very low, and its plasma concentration-time curve was also anomalous. Plasma concentration of the major metabolite was comparatively high, and the peak plasma concentration was 87.0 +/- 29.1 ng/ml. The T-max was late (7.85 +/- 1.62 h), and part of individual pharmacokinetic profiles showed double peaks, which indicated scutellarin could be absorbed into the intestine after hydrolysis to its aglycone by bacterial enzymes. This was followed by reconjugation in the intestinal cell and/or liver with glucuronic acid catalyzed by the phase II enzyme, which showed regioselectivity and species difference. The regioselectivity of glucuronoconjugation for scutellarin may be of importance for pharmacological activity. Plasma concentration of isoscutellarin can be used as a biomarker of scutellarin intake.
WOS关键词	GASTROINTESTINAL-TRACT ; HYDROGEN-PEROXIDE ; SMALL-INTESTINE ; RAT-LIVER ; IN-VITRO ; ABSORPTION ; QUERCETIN ; AGLYCONE ; ISOFLAVONES ; GLUCURONIDE
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
WOS记录号	WOS:000239073200010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273527]
专题	上海药物代谢研究中心
通讯作者	Zhong, Dafang
作者单位	1.Shenyang Pharmaceut Univ, Lab Drug Metab & Pharmacokinet, Shenyang, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Metab & Pharmacokinet Res, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Chen, Xiaoyan,Cui, Liang,Duan, Xiaotao,et al. Pharmacokinetics and metabolism of the flavonoid scutellarin in humans after a single oral administration[J]. DRUG METABOLISM AND DISPOSITION,2006,34(8):1345-1352.
APA	Chen, Xiaoyan,Cui, Liang,Duan, Xiaotao,Ma, Bin,&Zhong, Dafang.(2006).Pharmacokinetics and metabolism of the flavonoid scutellarin in humans after a single oral administration.DRUG METABOLISM AND DISPOSITION,34(8),1345-1352.
MLA	Chen, Xiaoyan,et al."Pharmacokinetics and metabolism of the flavonoid scutellarin in humans after a single oral administration".DRUG METABOLISM AND DISPOSITION 34.8(2006):1345-1352.